title: MIP-2A is a novel target of an anilinoquinazoline derivative for inhibition of tumour cell proliferation.
abstract: We recently identified a novel anilinoquinazoline derivative, Q15, as a potent apoptosis inducer in a panel of human cancer cell lines and determined that Q15 targets hCAP-G2, a subunit of condensin II complex, leading to abnormal cell division. However, whether the defect in normal cell division directly results in cell death remains unclear. Here, we used an mRNA display method on a microfluidic chip to search for other Q15-binding proteins. We identified an additional Q15-binding protein, MIP-2A (MBP-1 interacting protein-2A), which has been reported to interact with MBP-1, a repressor of the c-Myc promoter. Our results indicate that Q15 inhibits the interaction between MIP-2A and MBP-1 as well as the expression of c-Myc protein, thereby inducing cell death. This study suggests that the simultaneous targeting of hCAP-G2 and MIP-2A is a promising strategy for the development of antitumor drugs as a treatment for intractable tumours.
authors.affiliation: Department of Biosciences and Informatics, Keio University, Yokohama, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Tokunaga
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Shiheido
authors.forename: Noriko
authors.initials: N
authors.lastname: Tabata
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakuma-Yonemura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takashima
authors.forename: Kenichi
authors.initials: K
authors.lastname: Horisawa
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Doi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yanagawa
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000595:Amino Acid Sequence; D000814:Aniline Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D046210:Microfluidic Analytical Techniques; D008969:Molecular Sequence Data; D015394:Molecular Structure; D046912:Multiprotein Complexes / Q000378:metabolism; D011799:Quinazolines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; C088830:DENND4A protein, human; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; D046912:Multiprotein Complexes; D011799:Quinazolines; C120759:TRAPPC2 protein, human; D014157:Transcription Factors; C108312:condensin complexes; D000251:Adenosine Triphosphatases